We have recently shown that many patients who have chest pain despite insignificant coronary artery disease and absence of epicardial coronary artery spasm by ergonovine challenge exhibit abnormal coronary arteriolar vasodilator reserve in response to coronary sinus pacing. Ths abnormality can be unmasked or exacerbated by simulateneous cold pressor test or ergonovine infusion. To ascertain the effects of beta blocker and calcium antagonist therapy in this syndrome, 12 patients underwent graded upright bicycle exercise testing in a randomized, double-blind study comparing propranolol and verapamil to placebo. While verapamil had neither beneficial nor detrimental effects, propranolol impaired the exercise tolerance of these patients with chest pain and abnormal coronary arteriolar vasodilator reserve. The most likely mechanism responsible for this finding is the drug's capacity to reduce vasodilator reserve further by blocking coronary beta-2 adrenergic receptors.